Addiction to drugs like cocaine, nicotine and alcohol is often a chronic, relapsing disorder with serious consequences for the drug user and for society as a whole. Addiction can be very difficult to overcome, in part because addictive drugs rewire neural circuits involved in the brain's reward system. This can help form powerful memories of cues associated with drug use that include people, places, sights and sounds. Cue memory drives continued drug use as well as relapse when an addict is exposed to drug-associated cues. Scientists now report a way to erase cue memory in rats by pharmacologically interfering with the rewiring of the brain circuit that underlies its formation.

The treatment was developed by neuroscientists at The University of Texas at Austin led by Hitoshi Morikawa. They trained male Sprague Dawley rats to associate a compartment of a specific color (either black or white) with administration of cocaine or ethanol; once trained, the rats almost always chose to enter the compartment associated with the drug, when given a choice between two compartments.

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The researchers then infused the brains of the trained rats with a compound called isradipine before the rats made their choices. Isradipine is used to treat hypertension and is also being investigated for its potential to slow neurodegeneration in Parkinson's disease. When tested on the same day when they received the isradipine infusion, rats still chose the compartment associated with the drug, but when tested on the next two days, they no longer showed a preference for that compartment (Mol. Psychiatry doi:10.1038/mp.2015.84; published online 23). Even after two weeks of drug withdrawal, when the rats were exposed to the drug again and then given a choice between two compartments, those that received isradipine showed no preference for the compartment associated with the drug. “The isradipine erased memories that led them to associate a certain room with cocaine or alcohol,” said Morikawa in a press release.

Antihypertensive drugs like isradipine block a type of ion channel found in various cells including certain brain cells. Blocking these channels in the brain seemed to reverse the rewiring that underlies cue memory in rats, causing them to 'unlearn' the association between the drug and the compartment in which it was administered. “This drug might help the addicted brain become de-addicted,” Morikawa explained, although it remains to be seen whether the strategy will prove effective at counteracting addiction in humans.